Work

Ion interference induced by Ca-Mn nanoplatform enhances ferroptosis and promotes immune response for osteosarcoma treatment

Year: 2025

Type: article

Abstract: Introduction Ion interference therapy has emerged as a promising new treatment for Osteosarcoma (OS). However, its efficacy is significantly restricted by inadequate hydrogen peroxide (H 2 O 2 ) under the complex tumor microenvironment (TME). Objectives This study aimed to supply sufficient H 2 O 2 to enhance tumor therapy efficacy and address the limitations associated with ion interference. Methods A hollow manganese dioxide (HMnO 2 ) nanoplatform loaded with calcium peroxide (CaO 2 ) (denoted as HMnO 2 @CaO 2 ) was evaluated for biosafety through hemolysis tests. The functionality of HMnO 2 @CaO 2 was further validated by quantitative real-time polymerase chain reaction (qRT-PCR) and cytometric analysis. Results Excessive Ca 2+ accumulation induces endoplasmic reticulum (ER) stress, enhances oxidative stress, and causes mitochondrial damage. Notably, Mn 2+ facilitates treatment monitoring through magnetic resonance imaging (MRI). Additionally, Mn 2+ -induced ferroptosis triggers an immune response that promotes the polarization of tumor-associated macrophages (TAMs), transforming the pro-tumoral M2 phenotype into the tumoricidal M1 phenotype, thereby enhancing the efficacy of immunotherapy. Conclusion In conclusion, HMnO 2 @CaO 2 nanoplatform enhances tumor therapy efficacy by overcoming ferroptosis limitations, inducing Ca 2+ overload, and boosting anti-tumor immunity. This strategy offers a promising approach to ion interference in the clinical translation of nanomedicines. Furthermore, it marks a significant advancement in osteosarcoma (OS) treatment and underscores the transformative potential of nanotechnology in medicine.

Source: Journal of Advanced Research

DOI: 10.1016/j.jare.2025.06.022